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Study Liver Cytochrome P450 3A4 Inhibition and Hepatotoxicity Using DMSO-Differentiated HuH-7 Cells

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High-Throughput Screening Assays in Toxicology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1473))

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Abstract

Metabolically competent, inexpensive, and robust in vitro cell models are needed for studying liver drug-metabolizing enzymes and hepatotoxicity. Human hepatoma HuH-7 cells develop into a differentiated in vitro model resembling primary human hepatocytes after a 2-week dimethyl sulfoxide (DMSO) treatment. DMSO-treated HuH-7 cells express elevated cytochrome P450 3A4 (CYP3A4) enzyme gene expression and activity compared to untreated HuH-7 cells. This cell model could be used to study CYP3A4 inhibition by reversible and time-dependent inhibitors, including drugs, food-related substances, and environmental chemicals. The DMSO-treated HuH-7 model is also a suitable tool for investigating hepatotoxicity. This chapter describes a detailed methodology for developing DMSO-treated HuH-7 cells, which are subsequently used for CYP3A4 inhibition and hepatotoxicity studies.

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Correspondence to Yitong Liu .

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Liu, Y. (2016). Study Liver Cytochrome P450 3A4 Inhibition and Hepatotoxicity Using DMSO-Differentiated HuH-7 Cells. In: Zhu, H., Xia, M. (eds) High-Throughput Screening Assays in Toxicology. Methods in Molecular Biology, vol 1473. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6346-1_7

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  • DOI: https://doi.org/10.1007/978-1-4939-6346-1_7

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-6344-7

  • Online ISBN: 978-1-4939-6346-1

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